NCT01428193

Effects of Androgen Blockade on Sensitivity of the GnRH Pulse Generator to Suppression by Estradiol and Progesterone

Effect of Androgen Blockade on Sensitivity of the GnRH Pulse Generator to Suppression by Estradiol and Progesterone in Hyperandrogenic Adolescent Girls (JCM021)

• Status: Terminated
• Phase: N/A
• Study type: Interventional
• Enrollment: 4 (actual)
• Sponsor: University of Virginia · Academic / Other
• Sex: Female
• Age: 13 Years – 17 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to understand the effects of elevated male hormones in adolescent girls and how they effect the development of polycystic ovary syndrome (PCOS). If the investigators understand the effects of elevated male hormones levels in girls, the investigators may be able to better treat girls with elevated male hormone levels and perhaps even learn how to prevent the development of PCOS. Females with elevated levels of male hormones respond differently to estrace (estradiol) and progesterone than females with normal male hormone levels. The investigators will be giving you estrogen and progesterone to see how you respond after the male hormone has been blocked by a medication called flutamide.

Detailed description

Similar to women with PCOS, girls with hyperandrogenemia have an increased frequency of LH pulses when compared to age matched controls. An ongoing study by our group is investigating whether the progesterone insensitivity of the GnRH pulse generator in adult women with PCOS is also seen in adolescent girls with hyperandrogenemia. Analysis of the data to date suggests that the hyperandrogenic adolescent girls have decreased hypothalamic progesterone sensitivity when compared to adolescent controls, with a subgroup (consisting of approximately half of the hyperandrogenic girls) having marked progesterone insensitivity similar to that seen in adult women with PCOS. These data have recently been published. Given that androgens mediate hypothalamic progesterone insensitivity in adult women with PCOS, we hypothesize that androgens play a similar role in adolescent girls with hyperandrogenemia and that progesterone sensitivity can be restored with the use of the androgen receptor blocker flutamide. Better understanding the effects of hyperandrogenemia in adolescence and its role in the development of PCOS will hopefully lead to improved prevention and treatment strategies for PCOS. This may prove increasingly important if the current epidemic in childhood obesity results in a growing number of girls with elevated androgen levels.

Conditions

• Polycystic Ovary Syndrome
• Hyperandrogenism

Interventions

Type	Name	Description
DRUG	Flutamide	Subjects weighing \> 50 kg will receive 250 mg orally twice a day, and subjects weighing \< 50 kg will receive 125 mg orally twice a day.
DRUG	Progesterone	oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days
DRUG	estrace	0.5-1 mg once a day for seven days

Timeline

• Start date: 2006-09-01
• Primary completion: 2017-08-01
• Completion: 2017-08-01
• First posted: 2011-09-02
• Last updated: 2018-06-04
• Results posted: 2018-06-04

Locations

1 site across 1 country: United States